Microfluidics-Driven Fabrication of a Low Cost and Ultrasensitive SERS-Based Paper Biosensor

Surface-enhanced Raman scattering (SERS) spectroscopy stands out due to its sensitivity, selectivity, and multiplex ability. The development of ready-to-use, simple, and low-cost SERS substrates is one of the main challenges of the field. In this paper, the intrinsic reproducibility of microfluidics technology was used for the fabrication of self-assembled nanoparticle structures over a paper film. The paper SERS substrates were fabricated by assembling anisotropic particles, gold nanostars (GNSs), and nanorods (NRs) onto paper to offer an extra enhancement to reach ultra-sensitive detection limits. A polydimethylsiloxane PDMS-paper hybrid device was used to control the drying kinetics of the nanoparticles over the paper substrate. This method allowed a high reproducibility and homogeneity of the fabrication of SERS substrates that reach limits of detection down to the picomolar range. This simple and low-cost fabrication of a paper-based sensing device was tested for the discrimination of different cell lineages.